PMID- 22245561
OWN - NLM
STAT- MEDLINE
DCOM- 20120723
LR  - 20151119
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 62
IP  - 5-6
DP  - 2012 Apr
TI  - Long lasting effects of early-life stress on glutamatergic/GABAergic circuitry in 
      the rat hippocampus.
PG  - 1944-53
LID - 10.1016/j.neuropharm.2011.12.019 [doi]
AB  - The objective of the present work was to study the effects of an early-life 
      stress (maternal separation, MS) in the excitatory/inhibitory ratio as a 
      potential factor contributing to the ageing process, and the purported 
      normalizing effects of chronic treatment with the antidepressant venlafaxine. MS 
      induced depressive-like behaviour in the Porsolt forced swimming test that was 
      reversed by venlafaxine, and that persisted until senescence. Aged MS rats showed 
      a downregulation of vesicular glutamate transporter 1 and 2 (VGlut1 and VGlut2) 
      and GABA transporter (VGAT) and increased expression of excitatory amino acid 
      transporter 2 (EAAT2) in the hippocampus. Aged rats showed decreased expression 
      of glutamic acid decarboxylase 65 (GAD65), while the excitatory amino acid 
      transporter 1 (EAAT1) was affected only by stress. Glutamate receptor subunits 
      NR1 and NR2A and GluR4 were upregulated in stressed rats, and this effect was 
      reversed by venlafaxine. NR2B, GluR1 and GluR2/3 were not affected by either 
      stress or age. MS, both in young and aged rats, induced an increase in the 
      circulating levels of corticosterone. Corticosterone induced an increase 
      glutamate and a decrease in GABA release in hippocampal slices, which was 
      reversed by venlafaxine. Chronic treatment with corticosterone recapitulated the 
      main biochemical findings observed in MS. The different effects that chronic 
      stress exerts in young and adult animals on expression of proteins responsible 
      for glutamate/GABA cycling may explain the involvement of glucocorticoids in 
      ageing-related diseases. Modulation of glutamate/GABA release may be a relevant 
      component of the therapeutic action of antidepressants, such as venlafaxine.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Martisova, Eva
AU  - Martisova E
AD  - Department of Pharmacology, University of Navarra, C/ Irunlarrea 1, 31008 
      Pamplona, Spain.
FAU - Solas, Maite
AU  - Solas M
FAU - Horrillo, Igor
AU  - Horrillo I
FAU - Ortega, Jorge E
AU  - Ortega JE
FAU - Meana, J Javier
AU  - Meana JJ
FAU - Tordera, Rosa Maria
AU  - Tordera RM
FAU - Ramirez, Maria Javier
AU  - Ramirez MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120104
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Cyclohexanols)
RN  - 0 (Excitatory Amino Acid Transporter 1)
RN  - 0 (GABA Plasma Membrane Transport Proteins)
RN  - 0 (Slc1a3 protein, rat)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 7D7RX5A8MO (Venlafaxine Hydrochloride)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Antidepressive Agents, Second-Generation/pharmacology/therapeutic use
MH  - Corticosterone/blood
MH  - Cyclohexanols/pharmacology/therapeutic use
MH  - Depression/drug therapy/*metabolism/physiopathology
MH  - Excitatory Amino Acid Transporter 1/metabolism
MH  - Female
MH  - GABA Plasma Membrane Transport Proteins/metabolism
MH  - Glutamate Decarboxylase/metabolism
MH  - Glutamic Acid/*metabolism
MH  - Hippocampus/*metabolism/physiopathology
MH  - Male
MH  - *Maternal Deprivation
MH  - Nerve Net/*metabolism/physiopathology
MH  - Neurons/*metabolism
MH  - Rats
MH  - Venlafaxine Hydrochloride
MH  - gamma-Aminobutyric Acid/*metabolism
EDAT- 2012/01/17 06:00
MHDA- 2012/07/24 06:00
CRDT- 2012/01/17 06:00
PHST- 2011/08/03 00:00 [received]
PHST- 2011/12/14 00:00 [revised]
PHST- 2011/12/19 00:00 [accepted]
PHST- 2012/01/17 06:00 [entrez]
PHST- 2012/01/17 06:00 [pubmed]
PHST- 2012/07/24 06:00 [medline]
AID - S0028-3908(11)00576-4 [pii]
AID - 10.1016/j.neuropharm.2011.12.019 [doi]
PST - ppublish
SO  - Neuropharmacology. 2012 Apr;62(5-6):1944-53. doi: 
      10.1016/j.neuropharm.2011.12.019. Epub 2012 Jan 4.